Fever clinic construction and management targeted to prevention and control of healthcare-associated respiratory viral infections in Jiangsu, China: A cross-sectional observational study.

To analyze the post-COVID-19 construction and management of fever clinics targeted to prevention and control of healthcare-associated respiratory viral infections in medical institutions at all levels in China, and to provide a basis for promoting their standardized construction, we conducted this survey on the construction of fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020. Contents of the questionnaire included the general situation of medical institutions, the construction status and future construction plans of fever clinics. We find the construction rate of fever clinic in medical institutions of Jiangsu province was 75.3%. All construction indicators, quality management systems and processes fail to fully meet the requirements of documents and standards. Jiangsu province actively promotes the construction of fever clinic layout, but there is still a gap with the construction standard. As a result, it is necessary to further promote standardized construction of fever clinic, and necessary financial input should be increased to expand all constructions of fever clinic in primary medical institutions.

Short-term effect of particulate matter on lung function and impulse oscillometry system (IOS) parameters of chronic obstructive pulmonary disease (COPD) in Beijing, China.

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.

Isorhynchophylline ameliorates stress-induced emotional disorder and cognitive impairment with modulation of NMDA receptors.

Introduction: Isorhynchophylline is one of the main active ingredients from Uncaria rhynchophylla, the effects and mechanisms of isorhynchophylline on stress-induced emotional disorders and cognitive impairment remain unclear. Methods: Long-term potentiation (LTP) in vivo was used for synaptic plasticity evaluation; chronic unpredictable mild stress (CUMS) model was used to evaluate the effect of isorhynchophylline on stress induced emotional disorders and cognitive impairment; sucrose preference test (SPT), open field test (OFT), and elevated plus maze (EPM) were used to evaluate emotional disorders; morris water maze (MWM) test was used to evaluate cognitive impairment; Western blotting (WB) was used to the expression of proteins; high performance liquid chromatography (HPLC) was used to quantify neurotransmitters; Nissl staining was used to identify pathological changes induced by stress. Results: In this study, we found that isorhynchophylline improved corticosterone-induced in vivo LTP impairment significantly, indicating positive effects on stress. Therefore, 28-day CUMS model was adopted to evaluate the anti-stress effects of isorhynchophylline. The results showed that isorhynchophylline improved CUMS-induced weight loss, anxiety- and depression-like behaviors, and spatial memory impairment. Isorhynchophylline reduced CUMS-induced corticosterone elevation. N-methyl-D-aspartic acid (NMDA) receptors play an important role in the process of emotion and memory. Glutamate and the expression of GluN2B increased in the CUMS mice, while D-serine and the expression of serine racemase (SR) decreased significantly, and isorhynchophylline restored these changes to normal level. Conclusion: These results indicated that isorhynchophylline ameliorated stress-induced emotional disorders and cognitive impairment, modulating NMDA receptors might be one of the underlying mechanisms.

The Distribution and Source of MRDOs Infection: A Retrospective Study in 8 ICUs, 2013-2019.

BACKGROUND: To analyze the distribution and source of MDROs infection in the ICUs and to provide a basis for formulating more effective prevention and control programs for MDROs. METHODS: A retrospective investigation was conducted on MDROs infection in 8 ICUs of a large tertiary hospital from July 2013 to June 2019. A total of 2629 strains of MDROs isolated from 1701 inpatients were selected for analysis. The MDROs of the 8 ICUs were divided into two types of four categories according to source: out-of-hospital (out-of-hospital transfer and community acquisition) and in-hospital (in-hospital transfer and department acquisition) infections. RESULTS: CRAB (41.84%) and CRE (35.07%) accounted for the majority of the infecting MDROs. The detection rates of MRSA, CRAB, CRPA and CRE were 61.24%, 83.75%, 43.01% and 30.15%, respectively. The top three infection sites of MDROs were the lower respiratory tract (81.10%), blood (6.70%) and abdominal cavity (5.80%). The out-of-hospital and in-hospital infection rates of MDROs were 50.51% and 49.49%, respectively; the out-of-hospital infection rates for MRSA, CRAB, CRPA and CRE were 43.56%, 55.91, 64.44% and 44.58%, respectively. The proportions of MRSA, CRAB, CRPA and CRE infections contracted in the department were 40.98%, 36.27%, 25.56% and 46.62%, respectively. There was a statistically significant difference between comprehensive ICU and specialized ICU wards as sources for CRAB infections (P < 0.001). CONCLUSION: The main source of MDROs in the ICU is not the hospital itself entirely. It is particularly important to strengthen the identification of MDRO sources and implement more effective and accurate infection prevention and control measures.

Reduced D-Serine Release May Contribute to Impairment of Long-Term Potentiation by Corticosterone in the Perforant Path-Dentate Gyrus.

Long-term potentiation (LTP) is a neurobiological mechanism of cognitive function, and the N-methyl-D-aspartate (NMDA) receptors is fundamental for LTP. Previous studies showed that over activation of NMDA receptors may be a crucial cause of LTP and cognitive impairment induced by stress or corticosterone. However, other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment. The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms. Results showed that hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice. Corticosterone increased the glutamate level in hippocampal tissues, neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP, while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone, suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone. Further results showed that the level of D-serine and its precursor L-serine did not change. D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1 (ASC-1) in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone. Taken together, this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction, which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.

Evaluation of manual and electronic healthcare-associated infections surveillance: a multi-center study with 21 tertiary general hospitals in China.

BACKGROUND: Healthcare-associated infections (HAIs) are still a major health threats worldwide. Traditional surveillance methods involving manual surveillance by infection control practitioners (ICPs) for data collection processes are laborious, inefficient, and generate data of variable quality. In this study, we sought to evaluate the impact of surveillance and interaction platform system (SIPS) for HAIs surveillance compared to manual survey in tertiary general hospitals. METHODS: A large multi-center study including 21 tertiary general hospitals and 63 wards were performed to evaluate the impact of electronic SIPS for HAIs. RESULTS: We collected 4,098 consecutive patients and found that the hospitals installed with SIPS significantly increased work efficiency of ICPs achieving satisfactory diagnostic performance of HAIs with 0.73 for sensitivity, 0.81 for specificity and 0.81 area under the curve (AUC). However, there were significant heterogeneity own to regions, time of SIPS installation, departments and sample size. CONCLUSIONS: SIPS significantly improved ICPs efficiency and HAIs monitoring effectiveness, but there were shortcomings such as untimely maintenance and high cost.

Active fraction combination from Liuwei Dihuang decoction (LW-AFC) ameliorates corticosterone-induced long-term potentiation (LTP) impairment in mice in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LW), a classic formula in Traditional Chinese medicine (TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6 herbs including Dihuang (prepared root of Rehmannia glutinosa (Gaertn.) DC.), Shanyao (rhizome of Dioscorea polystachya Turcz.), Shanzhuyu (fruit of Cornus officinalis Siebold & Zucc.), Mudanpi (root bark of Paeonia × suffruticosa Andrews), Zexie (rhizome of Alisma plantago-aquatica L.) and Fuling (scleorotia of Wolfiporia extensa (Peck) Ginns). LW-active fraction combination (LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. Recent researches indicate that the "kidney deficiency" is related to a disturbance in the neuroendocrine immunomodulation (NIM) network, and glucocorticoids play an important role in kidney deficiency. AIM OF THE STUDY: This study evaluated the effects of LW-AFC and the active fractions (polysaccharide, LWB-B; glycoside, LWD-b; oligosaccharide, CA-30) on corticosterone (Cort)-induced long-term potentiation (LTP) impairment in vivo. MATERIALS AND METHODS: In this study, LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration (i.g., i.p., 7 days) or single administration (i.c.v., i.g., i.p.). Cort was injected subcutaneously 1 h before the high-frequency stimulation (HFS) to induce LTP impairment. Moreover, in order to research on the possible effective pathways, an antibiotic cocktail and an immunosuppressant were also used. RESULTS: Chronic administration (i.g.) of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Single administration (i.c.v., i.g., i.p.) of any of the active fractions had no effect on Cort-induced LTP impairment, while chronic administration (i.g., i.p.) of LWB-B or LWD-b showed positive effects against Cort. Interestingly, CA-30 only showed protective effects via i.g. administration, and there was little effect when CA-30 was administered i.p. In addition, when the intestinal microbiota was disrupted by application of the antibiotic cocktail, CA-30 showed little protective effects against Cort. The effects of LW-AFC were also abolished when the immune function was inhibited. In the hippocampal tissue, Cort treatment increased corticosterone and glutamate, and LW-AFC could inhibit the Cort-induced elevation of corticosterone and glutamate; there was little change in D-serine in Cort-treated animals, but LW-AFC could increase the D-serine levels. CONCLUSION: LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Their protective effects are unlikely by a direct way, and immune modulation might be the common pathway. CA-30 could protect LTP from impairment via modulating the intestinal microbiota. Decreasing corticosterone and glutamate and increasing D-serine in the Cort-treated animals' hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC. Further study is needed to understand the underlying mechanisms.

Interpretation and clinical practice of regulation for prevention and control of healthcare associated infection in outpatient and emergency department in healthcare facilities.

Healthcare associated infection (HAI) control and prevention is the important component of medical safety. Healthcare workers (HCWs) are the core forces for implementing good HAI control and prevention. Several cases of outbreaks occurred in outpatient and emergency department (OED) strengthened the importance of infection control and prevention. Recently, the "Regulation for prevention and control of HAI in outpatient and emergency department in healthcare facilities" was released by National health Commission of the People's Republic of China on May 10, 2018 and was going to implement on Nov 1, 2018. This regulation stipulates basic infection prevention requirements for safe care in OED of healthcare facilities. In this article, we would provide the interpretation and clinical practice of regulation for prevention and control of HAI in outpatient and emergency department in healthcare facilities and give a summary introduction.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology.

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant.

AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies.

Kainate receptor mediated presynaptic LTP in agranular insular cortex contributes to fear and anxiety in mice.

Anxiety disorders represent serious social problems worldwide. Recent neuroimaging studies have found that elevated activity and altered connectivity of the insular cortex might account for the negative emotional states in highly anxious individuals. However, the exact synaptic mechanisms of specific insular subregions have yet to be studied in detail. To assess the electrophysiological properties of agranular insular cortex (AIC) neurons, basic synaptic transmission was recorded and different protocols were used to induce presynaptic and postsynaptic long-term potentiation in mice with anxiety-related behaviors. The presynaptic membrane expression of kainate receptors (KARs) and pharmacologic manipulations were quantified to examine the role of Gluk1 subtype in anxiety-like behaviors. Fear conditioning occludes electrically induced postsynaptic-LTP in the AIC. Quantal analysis of LTP expression in this region revealed a significant presynaptic component reflected by an increase in the probability of transmitter release. A form of presynaptic-LTP that requires KARs has been characterized. Interestingly, a simple emotional anxiety stimulus resulted in selective occlusion of presynaptic-LTP, but not of postsynaptic-LTP. Finally, injecting GluK1-specific antagonists into the AIC reduced behavioral responses to fear or anxiety stimuli in the mouse. These findings suggest that activity-dependent synaptic plasticity takes place in the AIC due to exposure to fear or anxiety, and inhibiting the presynaptic KAR function may help to prevent or treat anxiety disorder.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial.

No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA) injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104) were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U) and two concentrations (50 U/mL or 100 U/mL). The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease.

BACKGROUND This study aimed to investigate the diagnostic values of serum levels of Hcy and UA for predicting vascular mild cognitive impairment (VMCI) in patients with cerebral small vessel disease (SVD). MATERIAL AND METHODS We selected 172 cerebral SVD patients and divided them into a VMCI group and a non-VMCI group. Eighty-six healthy individuals without nervous system diseases were selected as the control group. Enzymatic cycling method was performed to detect serum Hcy and UA levels. Serum levels of folic acid (FOA) and vitamin B12 (VitB12) were detected by chemiluminescence immunoassay. Montreal cognitive assessment (MoCA) was applied to evaluate the cognitive function. The ROC curve was used to evaluate the diagnostic values of serum Hcy and UA levels for predicting VMCI. Logistic regression analysis was used to determine the possible risk factors. RESULTS Compared with the non-VMCI and control groups, serum FOA and VitB12 levels were lower and serum Hcy and UA levels were higher in the VMCI group. AUC values of serum Hcy and UA levels were 0.703 and 0.829, respectively. Serum Hcy and UA levels were negatively correlated with serum FOA and VitB12 levels, total MoCA score, and subscores on visuospatial ability and executive function, on language ability and on delayed recall, and they were positively correlated with serum cholesterol (CH) level. Serum Hcy and UA levels were indicated as risk factors for VMCI in cerebral SVD patients. CONCLUSIONS These results suggest that serum Hcy and UA levels may serve as predictive factors for VMCI in cerebral SVD patients.

Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors Shows Positive Effects against Amyloid-ß-Induced Neurotoxicity.

Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-ß (Aß)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aß, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect. In Aß ICV-injected animals, the combination of ifenprodil and D-cycloserine (a co-activator of NMDRs similar to D-serine) led to greater improvement in behavior tests (nest building, novel object recognition, and Morris water maze) than ifenprodil (Morris water maze) or D-cycloserine (nest building) alone. Signal pathway analysis showed that Aß disturbed the GluN2A/GluN2B-related pathway. The ratio of GluN2A to GluN2B decreased in Aß-treated animals, and TORC dephosphorylation and ERK1/2 activation, which could be initiated by GluN2A, also decreased in the hippocampal tissues of Aß-treated animals. As a result, the activation of CREB and the content of brain-derived BDNF decreased. The combination of ifenprodil and D-cycloserine reversed the signal pathway more significantly than ifenprodil or D-cycloserine alone, indicating that Aß-induced toxicology was mediated both by functionally inhibiting GluN2A and enhancing GluN2B. These results indicate that enhancing synaptic NMDARs and inhibiting extrasynaptic NMDARs concurrently showed protective effects against Aß-induced neurotoxicity, suggesting that modulation of the balance between GluN2A and GluN2B could be a potential strategy for AD drug development and therapy.

[Spatio-temporal Evolution of Groundwater Vulnerability Based on Spatial Autocorrelation].

The distribution patterns of human activities affecting groundwater vulnerability vary with time. Studying the temporal and spatial changes in groundwater vulnerability, exploring the distribution characteristics of each period, and predicting the trends of development are important to formulate an effective development plan and reduce the risk of groundwater pollution at the same time. Based on the hydrogeological data as well as humanities and social data for 2004, 2010, and 2016 for the Chaoyang District of Beijing, a comprehensive evaluation model considering the human factors such as the land use types was established using the DRASTIC model. The spatiotemporal pattern of groundwater vulnerability was quantitatively characterized by calculating the Global Moran's Ⅰ and Getis-Ord Gi* index, and the distribution characteristics and variations in groundwater vulnerability were analyzed by the centroid of the G index and the standard deviation ellipse of the study area. The results indicate that in 2004, 2010, and 2016, the areas of high vulnerability have gradually reduced. The groundwater vulnerability in the study area shows a strong spatial aggregation; high concentration areas are mainly distributed in the northeast and southwest regions. The vulnerability of the northeast region has been decreasing each year, while the vulnerability of the northwest region has not changed much. The main reasons are the land use changes and the reductions in fertilizer use.

[Removal of 2,4-dichlorophenol in Underground Water by Stabilized Nano Zero-valent Iron].

To restrain the nano zero-valent iron (NZVI) in aqueous solution from being reunited and oxidized, this paper used sodium carboxymethyl starch (CMS), which is an environmentally friendly and cheap material, for coating and surface modification of NZVI so as to improve its dispersity and suspension property. Transmission Electron Microscope (TEM) and X-ray diffraction (XRD) were used to study the microstructure and components of the modified NZVI, and the 2,4-dichlorophenol 2,4-(DCP) removal efficiency was researched through chemical experiment. Experiments showed that the modified NZVI was about 80~100 nm in diameter, present as chain or dispersed particles. The main component was zero-valent iron, and it had strong reducibility. When the proportion of CMS was 80.00%, the suspension property was the best; The NZVI after CMS coating and surface modification retained the original activity. In the experiment investigating the removal effect of 2,4-DCP using different proportion of cladding, the same finding was obtained. When the CMS's proportion was 80%, the removal effect was the best, reaching up to 83.69%, and the dechlorination and degradation were apparent.

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAßPPswe/PS1ΔE9 transgenic mice.

BACKGROUND: Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer's disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAßPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD. METHODS: After treatment with a novel Liuwei Dihuang formula (LW-AFC), mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-ß (Aß) deposition, and Aß level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an enzyme-linked immunosorbent assay (ELISA) were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. Data between two groups were compared using a Student's t test. Comparison of the data from multiple groups against one group was performed using a one-way analysis of variance (ANOVA) followed by a Dunnett's post hoc test or a two-way repeated-measures analysis of variance with a Tukey multiple comparisons test. RESULTS: LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Aß deposition in the brain, and reduced the concentration of Aß1-42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+ T cells, and reduced CD4+CD25+Foxp3+ T cells in the spleen lymphocytes, downregulated interleukin (IL)-1ß, IL-2, IL-6, IL-23, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-α and -ß, and upregulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. CONCLUSIONS: LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic mice via the restoration of the NIM network to a greater extent than either memantine or donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.

Streptozotocin Induces Mild Cognitive Impairment at Appropriate Doses in Mice as Determined by Long-Term Potentiation and the Morris Water Maze.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and effective therapeutic drugs in the clinic are still lacking. Ideally, AD progression could be stopped at an early stage, such as at the mild cognitive impairment (MCI) stage. MCI refers to the clinical condition between normal aging and dementia. Patients with MCI experience memory loss but do not meet the criteria for the diagnosis of clinically probable AD. However, few MCI animal models have been established. Here, we used in vivo long-term potentiation (LTP) recording and the Morris water maze (MWM) to evaluate the effects of intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. We found a relationship between cognitive behavior and LTP in vivo and determined the appropriate doses of STZ for a putative MCI animal model. Animals that received≥150µg of STZ exhibited cognitive impairment in the MWM test, and few changes in behavior tests were observed in animals receiving less than 150µg of STZ. In vivo LTP recordings revealed that the induction of LTP decreased significantly in STZ-treated animals, even at the lowest dose (25µg/mouse), in a dose-dependent manner. Pathology analysis revealed STZ-induced neuron loss in a dose-dependent manner, both in the cortex and in the hippocampus, as evidenced by a significantly decreased neuronal number in the cohort treated with 75µg of STZ/mouse. Our study indicated that a low dose (25µg/mouse) of STZ impaired neural plasticity; at a higher dose of 75µg/mouse STZ, further LTP deficits were noted along with induced neuronal loss in both the cortex and the hippocampus, which could be considered a possible MCI or pre-MCI animal model; and finally, at 150µg/mouse STZ, dementia was induced, feasibly indicating a state of AD.

Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo.

Early studies with first-generation poly (ADP-ribose) polymerase (PARP) inhibitors have already indicated some therapeutic potential for sulfur mustard (SM) injuries. The available novel and more potential PARP inhibitors, which are undergoing clinical trials as drugs for cancer treatment, bring it back to the centre of interest. However, the role of PARP-1 in SM-induced injury is not fully understood. In this study, we selected a high potent specific PARP inhibitor ABT-888 as an example to investigate the effect of PARP inhibitor in SM injury. The results showed that in both the mouse ear vesicant model (MEVM) and HaCaT cell model, PARP inhibitor ABT-888 can reduce cell damage induced by severe SM injury. ABT-888 significantly reduced SM induced edema and epidermal necrosis in MEVM. In the HaCaT cell model, ABT-888 can reduce SM-induced NAD(+)/ATP depletion and apoptosis/necrosis. Then, we studied the mechanism of PARP-1 in SM injury by knockdown of PARP-1 in HaCaT cells. Knockdown of PARP-1 protected cell viability and downregulated the apoptosis checkpoints, including p-JNK, p-p53, Caspase 9, Caspase 8, c-PARP and Caspase 3 following SM-induced injury. Furthermore, the activation of AKT can inhibit autophagy via the regulation of mTOR. Our results showed that SM exposure could significantly inhibit the activation of Akt/mTOR pathway. Knockdown of PARP-1 reversed the SM-induced suppression of the Akt/mTOR pathway. In summary, the results of our study indicated that the protective effects of downregulation of PARP-1 in SM injury may be due to the regulation of apoptosis, necrosis, energy crisis and autophagy. However, it should be noticed that PARP inhibitor ABT-888 further enhanced the phosphorylation of H2AX (S139) after SM exposure, which indicated that we should be very careful in the application of PARP inhibitors in SM injury treatment because of the enhancement of DNA damage.

Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAßPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment.

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAßPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1ß, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug.